This is an application for the Paul B. Beeson Career Development Award in Aging. Mild cognitive impairment (MCI) is a heterogeneous condition with multiple etiologies, presentations, and outcomes. This prospective study will investigate whether baseline magnetic resonace imaging (MRI) markers can predict conversion of MCI to Alzheimer disease (AD). We propose that entorhinal/parahippocampal, inferior and lateral temporal, posterior cingulate and precuneal gray matter atrophy, hippocampal atrophy and lateral ventricle enlargement will strongly correlate with conversion to AD within 3 years. We will recruit 90 MCI subjects from identified available recourses. They will receive a baseline high-quality structural MRI scan and yearly clinical and neuropsychological testing. The proposed state-of-the-art surface-based algorithms for explicit matching of corresponding morphology will reduce inter-subject variability, and increase the power to detect localized disease effects. The long-term goal of this project is to influence the methods of trial planning and patient selection, and to establish a powerful surrogate marker for MCI therapeutic trials. The candidate, Liana G. Apostolova, M.D., has developed an integrated research/educational plan that will lead to advanced knowledge in structural and functional neuroimaging analysis. In addition, she will pursue a Master of Science in Clinical Research degree at UCLA with structured course work in clinical trial methodology, biostatistics, clinical pharmacology and ethics of patient-oriented research. This multidisciplinary training will facilitate Dr. Apostolova's development into an independent investigator in patient-oriented research in aging. It will allow her to develop an R01 proposal investigating the effects of disease-modifying therapeutic interventions in a selected high-risk MCI cohort predestined to develop AD where MRI markers serve as surrogate marker of disease effect.